To determine which dosage of estrogen might provide physiologic replacement while minimizing adverse effects, 20 postmenopausal women were studied before and after oral administration of ethinyl estradiol. Twenty premenopausal women studied in the early and late follicular phases of the menstrual cycle were presumed to reflect normal physiologic function. Variable responses of the different biochemical and biologic markers to the actions of ethinyl estradiol were observed. Liver protein synthesis was the most sensitive measure of the action of ethinyl estradiol. In comparing the relative potencies of ethinyl estradiol with previously reported results observed with the usage of conjugated equine estrogens, the actions of 10 micrograms ethinyl estradiol were approximately equivalent to the biologic effects of 1.25 mg conjugated estrogens. The results suggest that ethinyl estradiol is far more potent than previously believed and that the daily administration of 10 micrograms, a dose lower than currently available commercial preparations, may be adequate for relief of symptoms of vaginal atrophy and may provide protection from the occurrence of osteoporotic fractures.